Data is available on Synapse.

Summary

This includes code and plots for the final version of the paper. Exploratory analysis and intermediate processing steps are too extensive to be included here

## Warning: replacing previous import 'igraph::union' by 'GSEABase::union'
## when loading 'HTSanalyzeR'

Sendai Expression

Biotype of expressed genes

Biotype Count
protein_coding 11681
processed_transcript 1691
antisense 1488
lincRNA 879
processed_pseudogene 822
nonsense_mediated_decay 708
retained_intron 671
sense_intronic 197
unprocessed_pseudogene 163
sense_overlapping 93
miRNA 66
misc_RNA 58
snoRNA 56
transcribed_unprocessed_pseudogene 47
pseudogene 37
transcribed_processed_pseudogene 28
snRNA 27
unitary_pseudogene 16
3prime_overlapping_ncrna 12
rRNA 8
Mt_tRNA 4
polymorphic_pseudogene 4
non_stop_decay 3
IG_V_pseudogene 1
TR_C_gene 1

Check sex on 94 samples

genes_on_chrY

USP9Y
UTY
NLGN4Y
ZFY
RPS4Y1
TXLNG2P

Detect sample contamination with VerifyBamID

The labeling of Donor 499 was corrected manually

Excluded due to sample mislabeling, contamination or issues with expression on the sex chromosomes

Sample.Name
1275-B-3F
1275-B-3N
1275-C-1F
1275-C-1N
2476-1-4F
2476-1-4N
2484-2aF
2484-2aN
3113-3-21F
3113-3-21N
3121-2-1F
3121-2-1N
3121-2-MSSM2F
3121-2-MSSM2N
3130-2-1F
3130-2-1N
676-1-2N

Samples included in analysis

6_wk_FB_neuron NPC
CT 20 20
SZ 19 18
Case Control
10 9

QC metrics

Check sex on cleaned dataset

Differential gene expression based on Sendai virus exression

[1] “DE genes at FDR < 5%: 2768”

Yaminaka factors

POU5F1 is not expressed at a sufficient level

logFC AveExpr t P.Value qvalue gene
ENSG00000136997 0.3021708 3.1929949 2.1221004 0.0371472 0.0849684 MYC
ENSG00000181449 -0.0561620 8.7614381 -1.0330145 0.3049324 0.2815826 SOX2
ENSG00000136826 -0.1388002 0.0752657 -0.8533798 0.3961789 0.3249660 KLF4

Compare Neurons and NPC

Enrichments for genes up in Neurons

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
tissue_exp_brain 495.00 65.97 241 3.65 9.20E-84
c2.BENPORATH_ES_WITH_H3K27ME3 730.00 97.29 283 2.91 2.29E-70
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347.00 46.25 162 3.50 7.81E-53
c2.BENPORATH_SUZ12_TARGETS 664.00 88.50 240 2.71 9.40E-53
c2.BENPORATH_EED_TARGETS 705.00 93.96 240 2.55 2.13E-47
c2.BENPORATH_PRC2_TARGETS 391.00 52.11 163 3.13 5.01E-45
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225.00 163.27 340 2.08 1.26E-44
c2.MIKKELSEN_MCV6_HCP_WITH_H3K27ME3 285.00 37.98 129 3.40 2.42E-40
c2.MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3 215.00 28.65 108 3.77 3.83E-39
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMBRANE 998.00 133.01 282 2.12 3.13E-38
c5.GO_CELL_CELL_SIGNALING 502.00 66.91 173 2.59 7.35E-35
c5.GO_NEURON_PART 1088.00 145.01 282 1.94 5.04E-31
c2.MIKKELSEN_NPC_HCP_WITH_H3K27ME3 192.00 25.59 90 3.52 7.31E-30
c2.NABA_MATRISOME 555.00 73.97 174 2.35 2.58E-29
c5.GO_SYNAPSE 677.00 90.23 198 2.19 7.62E-29
c5.GO_SYNAPTIC_SIGNALING 331.00 44.11 123 2.79 1.94E-28
c2.ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY 873.00 116.35 235 2.02 2.55E-28
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223.00 29.72 96 3.23 3.72E-28
tissue_exp_testis 452.00 60.24 149 2.47 9.65E-28
c5.GO_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY 298.00 39.72 112 2.82 1.80E-26

Enrichments for genes up in NPCs

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP 547 33.21 260 7.83 4.96E-176
c2.DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP 304 18.46 190 10.29 1.04E-156
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 41.89 247 5.90 7.73E-131
c2.KOBAYASHI_EGFR_SIGNALING_24HR_DN 236 14.33 153 10.68 6.86E-129
c4.MODULE_54 241 14.63 150 10.25 2.58E-122
c2.ROSTY_CERVICAL_CANCER_PROLIFERATION_CLUSTER 137 8.32 111 13.34 2.69E-111
c7.GSE15750_DAY6_VS_DAY10_TRAF6KO_EFF_CD8_TCELL_UP 186 11.29 122 10.80 3.20E-103
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_UP 1176 71.40 282 3.95 6.11E-101
c2.SHEDDEN_LUNG_CANCER_POOR_SURVIVAL_A6 416 25.26 170 6.73 6.49E-99
c7.GSE15750_DAY6_VS_DAY10_EFF_CD8_TCELL_UP 189 11.48 119 10.37 1.86E-97
c5.GO_CHROMOSOME 778 47.24 226 4.78 2.87E-97
c2.CHANG_CYCLING_GENES 145 8.80 103 11.70 1.19E-92
c5.GO_CHROMOSOME_ORGANIZATION 875 53.13 233 4.39 8.60E-92
c2.SOTIRIOU_BREAST_CANCER_GRADE_1_VS_3_UP 147 8.93 102 11.43 4.80E-90
c2.ZHANG_TLX_TARGETS_60HR_DN 263 15.97 131 8.20 3.32E-89
c2.REACTOME_CELL_CYCLE 384 23.31 155 6.65 6.43E-89
h.HALLMARK_E2F_TARGETS 199 12.08 115 9.52 5.45E-88
c2.PUJANA_BRCA2_PCC_NETWORK 388 23.56 153 6.49 5.80E-86
c7.GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_12H_UP 171 10.38 105 10.11 3.42E-84
c2.WHITEFORD_PEDIATRIC_CANCER_MARKERS 110 6.68 86 12.88 1.49E-83

Overlap between NPC and neuron

## [1] "cutoff: log2 RPKM > 0"

## [1] "cutoff: log2 RPKM > 1"

## [1] "cutoff: log2 RPKM > 2"

## [1] "cutoff: log2 RPKM > 3"

## [1] "cutoff: log2 RPKM > 4"

## [1] "cutoff: log2 RPKM > 5"

## [1] "cutoff: log2 RPKM > 6"

Cibersort results

Histogram of cell type composition: all samples

There is no case-control difference in cell type scores

Cell composition in Neurons and NPC

Differential expression based on cell fraction

Enrichment test for gene positively correlated with cell fraction

6_wk_FB_neuron-Astrocytes
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
CMC-modules_peru 114 68 108 1.6 3.3e-18
CMC-modules_lightgreen 199 118 173 1.5 8.7e-18
c4.MODULE_1 318 189 253 1.3 7.0e-15
c2.LEE_BMP2_TARGETS_UP 598 355 443 1.2 9.2e-15
c4.MODULE_47 196 116 162 1.4 1.4e-12
c5.GO_EXTRACELLULAR_STRUCTURE_ORGANIZATI 220 130 179 1.4 1.6e-12
c2.MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H 826 490 584 1.2 1.9e-12
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSI 177 105 148 1.4 2.1e-12
c4.MODULE_2 328 195 252 1.3 1.0e-11
c2.BOQUEST_STEM_CELL_UP 207 123 168 1.4 1.1e-11
6_wk_FB_neuron-Neuron
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 339 438 1.3 3.1e-26
CMC-modules_red 689 472 566 1.2 9.5e-17
CMC-modules_blue 1154 791 902 1.1 2.7e-14
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 238 294 1.2 2.0e-12
c5.GO_SYNAPTIC_SIGNALING 331 227 278 1.2 6.5e-11
c5.GO_CELL_CELL_SIGNALING 502 344 403 1.2 1.3e-09
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 113 146 1.3 1.4e-09
abnormal_synaptic_transmission 386 264 315 1.2 3.1e-09
secondary_FMRP-targets 770 528 599 1.1 3.1e-09
c5.GO_SYNAPSE 677 464 530 1.1 5.0e-09
6_wk_FB_neuron-Oligodendrocyte_Precursor_Cell
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 780 920 1.2 3.9e-19
CMC-modules_peru 114 73 108 1.5 3.8e-15
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 348 430 1.2 1.1e-14
c2.MILI_PSEUDOPODIA_HAPTOTAXIS_DN 626 399 483 1.2 9.2e-14
c5.GO_PROTEIN_COMPLEX_SUBUNIT_ORGANIZATI 1299 827 947 1.1 1.1e-13
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223 142 189 1.3 1.7e-12
c2.LU_AGING_BRAIN_UP 239 152 199 1.3 1.5e-11
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 253 313 1.2 2.6e-11
c5.GO_ENDOPLASMIC_RETICULUM 1285 818 924 1.1 4.4e-11
c5.GO_ENDOPLASMIC_RETICULUM_PART 926 590 679 1.2 7.9e-11
6_wk_FB_neuron-Fibroblast
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.REN_ALVEOLAR_RHABDOMYOSARCOMA_DN 391 279 352 1.3 6.4e-20
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 873 992 1.1 3.3e-16
CMC-modules_lightcyan 268 191 243 1.3 4.7e-15
c2.BLALOCK_ALZHEIMERS_DISEASE_UP 1486 1059 1182 1.1 1.5e-14
c5.GO_ENDOPLASMIC_RETICULUM 1285 916 1027 1.1 1.0e-13
c5.GO_ENDOPLASMIC_RETICULUM_PART 926 660 752 1.1 5.4e-13
c4.MODULE_1 318 227 278 1.2 3.4e-12
c4.MODULE_47 196 140 178 1.3 1.6e-11
c5.GO_MOVEMENT_OF_CELL_OR_SUBCELLULAR_CO 951 678 765 1.1 1.6e-11
c5.GO_LOCOMOTION 785 560 636 1.1 8.5e-11
6_wk_FB_neuron-MEF
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c5.GO_POLY_A_RNA_BINDING 1113 806 971 1.2 4.9e-35
c5.GO_RNA_BINDING 1466 1061 1240 1.2 5.2e-31
c5.GO_RIBONUCLEOPROTEIN_COMPLEX 660 478 595 1.2 2.0e-30
c4.MODULE_83 308 223 297 1.3 3.5e-29
pli_MID 2881 2086 2313 1.1 3.2e-27
c2.HSIAO_HOUSEKEEPING_GENES 374 271 350 1.3 5.8e-26
c4.MODULE_114 319 231 301 1.3 3.1e-24
c5.GO_RIBONUCLEOPROTEIN_COMPLEX_BIOGENES 419 303 384 1.3 2.3e-23
c4.MODULE_151 298 216 281 1.3 1.5e-22
c5.GO_RNA_PROCESSING 781 565 674 1.2 1.4e-21
6_wk_FB_neuron-Myocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c5.GO_RNA_BINDING 1466 996 1243 1.2 1.4e-53
c5.GO_POLY_A_RNA_BINDING 1113 756 964 1.3 5.4e-50
c5.GO_RIBONUCLEOPROTEIN_COMPLEX 660 449 589 1.3 3.1e-39
c2.PUJANA_BRCA1_PCC_NETWORK 1476 1003 1215 1.2 6.5e-39
CMC-modules_brown 897 610 766 1.3 7.2e-35
c4.MODULE_83 308 209 295 1.4 1.3e-34
c5.GO_RNA_PROCESSING 781 531 675 1.3 3.1e-34
c4.MORF_UBE2I 236 160 231 1.4 1.8e-32
c4.MODULE_114 319 217 302 1.4 2.3e-32
c4.MORF_CSNK2B 286 194 274 1.4 2.7e-32
6_wk_FB_neuron-hiPSC
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 347 507 1.5 7.3e-37
c2.MANALO_HYPOXIA_DN 279 140 240 1.7 1.0e-36
c5.GO_CHROMOSOME_ORGANIZATION 875 441 614 1.4 1.5e-34
c2.PUJANA_CHEK2_PCC_NETWORK 730 368 522 1.4 9.8e-33
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 275 404 1.5 2.8e-30
c5.GO_CHROMOSOME 778 392 544 1.4 5.5e-30
c2.PUJANA_BRCA1_PCC_NETWORK 1476 743 949 1.3 6.1e-30
c2.DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP 304 153 244 1.6 1.1e-27
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 616 797 1.3 1.5e-27
c2.LEE_BMP2_TARGETS_DN 826 416 564 1.4 6.8e-27
NPC-Astrocytes
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 320 402 1.3 2.2e-16
secondary_FMRP-targets 770 499 597 1.2 2.3e-15
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMB 998 646 731 1.1 1.9e-09
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 1000 647 730 1.1 5.2e-09
c5.GO_REGULATION_OF_NEUROTRANSMITTER_LEV 165 107 140 1.3 5.8e-09
c5.GO_NEURON_PART 1088 704 790 1.1 6.0e-09
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 793 883 1.1 7.5e-09
c5.GO_SYNAPTIC_SIGNALING 331 214 261 1.2 1.2e-08
c2.BENPORATH_ES_WITH_H3K27ME3 730 473 541 1.1 1.8e-08
c4.MODULE_66 474 307 361 1.2 3.5e-08
NPC-Neuron
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 279 399 1.4 5.9e-31
c2.BENPORATH_ES_WITH_H3K27ME3 730 411 507 1.2 7.2e-14
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 224 294 1.3 1.0e-13
secondary_FMRP-targets 770 434 528 1.2 7.2e-13
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 93 136 1.5 8.7e-13
c2.BENPORATH_SUZ12_TARGETS 664 374 455 1.2 3.5e-11
CMC-modules_blue 1154 650 754 1.2 6.6e-11
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 196 253 1.3 8.6e-11
CMC-modules_red 689 388 468 1.2 1.4e-10
c5.GO_NEURON_PART 1088 613 711 1.2 2.3e-10
NPC-Oligodendrocyte_Precursor_Cell
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
secondary_FMRP-targets 770 498 586 1.2 2.1e-12
c5.GO_CELL_PROJECTION 1508 976 1088 1.1 6.9e-11
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 1000 647 733 1.1 1.4e-09
c5.GO_NEURON_PROJECTION 835 540 614 1.1 1.4e-08
c5.GO_VACUOLE 959 621 699 1.1 1.6e-08
c5.GO_GOLGI_APPARATUS 1210 783 866 1.1 8.4e-08
c5.GO_NEURON_PART 1088 704 782 1.1 1.2e-07
primary_PSD_(human_core) 644 417 477 1.1 1.4e-07
c2.BERENJENO_TRANSFORMED_BY_RHOA_DN 365 236 281 1.2 2.1e-07
c5.GO_CELL_SUBSTRATE_JUNCTION 371 240 285 1.2 2.4e-07
NPC-Newly_Formed_Oligodendrocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
tissue_exp_brain 495 284 415 1.5 1.7e-37
c2.BENPORATH_ES_WITH_H3K27ME3 730 419 557 1.3 7.4e-28
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 199 283 1.4 4.0e-22
c2.BENPORATH_SUZ12_TARGETS 664 381 494 1.3 1.1e-20
c2.MIKKELSEN_MCV6_HCP_WITH_H3K27ME3 285 164 235 1.4 8.9e-20
c2.BENPORATH_PRC2_TARGETS 391 224 306 1.4 1.4e-18
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANC 397 228 308 1.4 1.1e-17
tissue_exp_testis 452 259 342 1.3 1.6e-16
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 703 837 1.2 2.1e-16
c5.GO_INTRINSIC_COMPONENT_OF_PLASMA_MEMB 998 573 687 1.2 1.2e-14
NPC-Fibroblast
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.NABA_MATRISOME 555 306 397 1.3 6.9e-16
c2.WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216 297 164 230 1.4 7.1e-16
Peptide_chain_elongation 82 45 77 1.7 6.5e-15
c2.REACTOME_PEPTIDE_CHAIN_ELONGATION 84 46 78 1.7 2.4e-14
Eukaryotic_Translation_Elongation 84 46 78 1.7 2.4e-14
Formation_of_a_pool_of_free_40S_subunit 92 51 84 1.7 3.2e-14
Viral_mRNA_Translation 83 46 77 1.7 4.1e-14
viral transcription 82 45 76 1.7 6.9e-14
c2.LEE_BMP2_TARGETS_UP 598 330 417 1.3 9.2e-14
3’_-UTR-mediated_translational_regulati 102 56 90 1.6 5.5e-13
NPC-MEF
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c4.MORF_RAD23A 343 240 319 1.3 3.2e-26
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 483 599 1.2 3.6e-26
c4.MORF_BUB3 275 193 261 1.4 1.4e-25
c2.PUJANA_BRCA1_PCC_NETWORK 1476 1034 1194 1.2 2.3e-23
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 824 967 1.2 2.7e-23
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 383 479 1.2 6.6e-23
c4.MORF_CSNK2B 286 200 266 1.3 4.6e-22
c2.DIAZ_CHRONIC_MEYLOGENOUS_LEUKEMIA_UP 1312 919 1061 1.2 1.2e-20
c2.SOTIRIOU_BREAST_CANCER_GRADE_1_VS_3_U 147 103 145 1.4 3.0e-20
c2.KOBAYASHI_EGFR_SIGNALING_24HR_DN 236 165 221 1.3 1.4e-19
NPC-Myocyte
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.PUJANA_BRCA1_PCC_NETWORK 1476 754 1005 1.3 3.9e-44
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 625 854 1.4 1.2e-43
c2.PUJANA_CHEK2_PCC_NETWORK 730 373 546 1.5 2.9e-41
CMC-modules_black 625 319 474 1.5 1.6e-38
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 600 810 1.3 4.7e-38
c2.CAIRO_HEPATOBLASTOMA_CLASSES_UP 581 297 434 1.5 1.2e-32
c2.JOHNSTONE_PARVB_TARGETS_3_DN 862 440 598 1.4 2.5e-29
c2.RODRIGUES_THYROID_CARCINOMA_POORLY_DI 604 308 440 1.4 6.5e-29
c2.LEE_BMP2_TARGETS_DN 826 422 575 1.4 7.9e-29
c4.GNF2_EIF3S6 118 60 114 1.9 1.6e-28
NPC-hiPSC
Gene.Set Gene.Set.Size Expected.Hits Observed.Hits OR Pvalue
c2.PUJANA_BRCA1_PCC_NETWORK 1476 850 1123 1.3 1.2e-54
c2.KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_U 1176 678 913 1.3 1.0e-50
c2.PUJANA_CHEK2_PCC_NETWORK 730 421 593 1.4 9.3e-44
c2.GOBERT_OLIGODENDROCYTE_DIFFERENTIATIO 547 315 460 1.5 1.1e-41
c2.MARSON_BOUND_BY_E2F4_UNSTIMULATED 690 398 559 1.4 1.4e-40
c2.DODD_NASOPHARYNGEAL_CARCINOMA_DN 1224 705 914 1.3 2.4e-38
c2.PUJANA_BRCA2_PCC_NETWORK 388 224 337 1.5 9.6e-37
c2.CAIRO_HEPATOBLASTOMA_CLASSES_UP 581 335 473 1.4 2.0e-35
Cell_Cycle 455 262 382 1.5 2.1e-34
h.HALLMARK_E2F_TARGETS 199 115 188 1.6 1.5e-32

Analysis of original data

Analysis after correcting for cell type composition scores for fibroblasts and MEF

Color PCA by CTC score

Correlation of CTC scores with principal components

## Projected run time: ~ 1 min

all cell fractions

accounting for MEF and Fibroblast increases donor contributions

## Projected run time: ~ 1 min
## Projected run time: ~ 1 min
## 
##  Paired t-test
## 
## data:  df$adjusted and df$original
## t = 15.713, df = 18909, p-value < 2.2e-16
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  0.003048520 0.003917501
## sample estimates:
## mean of the differences 
##             0.003483011

Percent bars

VariancePartition within each cell type

Compare donor effect

variancePartition: include technical variables

## Projected run time: ~ 4 min

Correlation between covariates

Differential expression between cases and controls in combined NPC + neuron dataset

Volcano plot

Genes with FDR < 20%

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -3.8867431 -2.0458924 -7.503823 0.0000000 0.0000021 ENSG00000230847
ENSG00000164930 -0.7773348 4.8643554 -5.911893 0.0000001 0.0008885 FZD6
ENSG00000226259 -1.1458273 2.3980778 -5.496058 0.0000005 0.0032175 GTF2H2B
ENSG00000236725 -1.0340737 0.4658067 -5.316601 0.0000011 0.0040039 ENSG00000236725
ENSG00000269337 -1.0984407 0.7260166 -5.313372 0.0000011 0.0040039 ENSG00000269337
ENSG00000169629 -0.9328454 2.8967989 -4.990793 0.0000039 0.0118105 RGPD8
ENSG00000184988 -0.6371885 0.6108187 -4.752049 0.0000097 0.0201639 TMEM106A
ENSG00000177873 -0.4751565 3.6251045 -4.744838 0.0000100 0.0201639 ZNF619
ENSG00000145246 0.8099405 3.4869808 4.737294 0.0000103 0.0201639 ATP10D
ENSG00000121691 1.5711365 4.3941262 4.717053 0.0000111 0.0201639 CAT
ENSG00000003402 -1.2184673 2.9784138 -4.658510 0.0000138 0.0228447 CFLAR
ENSG00000173894 0.3974699 5.3493957 4.539741 0.0000215 0.0325994 CBX2
ENSG00000237945 -1.4449894 3.0295611 -4.474223 0.0000273 0.0383219 LINC00649
ENSG00000037757 -1.0264047 3.0641913 -4.421709 0.0000332 0.0408592 MRI1
ENSG00000115828 -1.4442631 0.6431161 -4.417693 0.0000336 0.0408592 QPCT
ENSG00000181234 3.9832515 -0.9565400 4.375613 0.0000392 0.0446556 TMEM132C
ENSG00000164669 -0.9330823 -0.2461149 -4.356789 0.0000420 0.0450032 INTS4L1
ENSG00000240342 -0.6669021 4.8380931 -4.336412 0.0000452 0.0457606 RPS2P5
ENSG00000229404 -1.7586482 -0.9581430 -4.311301 0.0000495 0.0471821 LINC00858
ENSG00000254353 -2.1384802 -0.4100724 -4.291721 0.0000531 0.0471821 ENSG00000254353
ENSG00000226002 0.5981007 0.1750937 4.285220 0.0000544 0.0471821 ENSG00000226002
ENSG00000244026 -0.5236215 3.8687373 -4.177683 0.0000799 0.0661458 FAM86DP
ENSG00000185985 2.7724325 5.1279631 4.162363 0.0000843 0.0668031 SLITRK2
ENSG00000236383 -0.6271087 -0.4722674 -4.146970 0.0000891 0.0676050 LINC00854
ENSG00000229789 -1.2992945 -0.2195011 -4.131695 0.0000940 0.0684996 ENSG00000229789
ENSG00000010704 -0.9534242 -0.6692788 -4.104042 0.0001036 0.0717645 HFE
ENSG00000228463 -1.3430626 -0.4915192 -4.096619 0.0001064 0.0717645 ENSG00000228463
ENSG00000115507 1.9964444 -0.0009156 4.075118 0.0001147 0.0733737 OTX1
ENSG00000239959 -0.7577011 -0.1855192 -4.069923 0.0001168 0.0733737 ENPP7P2
ENSG00000162618 -1.6783969 -0.7365519 -4.043841 0.0001279 0.0741853 ELTD1
ENSG00000198715 -0.6225848 2.0519971 -4.037013 0.0001310 0.0741853 C1orf85
ENSG00000107829 -0.5636433 1.8306642 -4.028719 0.0001349 0.0741853 FBXW4
ENSG00000196569 -1.2655757 3.3493015 -4.027240 0.0001356 0.0741853 LAMA2
ENSG00000221870 2.5063090 1.4534521 4.021192 0.0001385 0.0741853 TMEM257
ENSG00000227775 0.4286190 4.0581385 3.993127 0.0001526 0.0794408 ENSG00000227775
ENSG00000160789 -0.3087472 6.1850559 -3.945999 0.0001796 0.0896624 LMNA
ENSG00000212719 -2.8235614 2.0022500 -3.938600 0.0001842 0.0896624 C17orf51
ENSG00000259085 0.4518444 0.8237710 3.934224 0.0001870 0.0896624 ENSG00000259085
ENSG00000137962 -0.8405123 5.9505584 -3.925476 0.0001927 0.0900281 ARHGAP29
ENSG00000148942 -1.7992311 -0.7765750 -3.905677 0.0002063 0.0939415 SLC5A12
ENSG00000234431 -1.1610396 -0.0453674 -3.836649 0.0002609 0.1159417 ENSG00000234431
ENSG00000106868 -0.4221252 5.3831940 -3.801357 0.0002940 0.1275207 SUSD1
ENSG00000256043 -1.1396397 2.1885944 -3.734748 0.0003676 0.1502070 CTSO
ENSG00000183036 1.0568761 0.2824591 3.731252 0.0003719 0.1502070 PCP4
ENSG00000255983 -1.7770246 -1.6255799 -3.724899 0.0003799 0.1502070 ENSG00000255983
ENSG00000108946 -0.1539076 8.5710566 -3.720296 0.0003857 0.1502070 PRKAR1A
ENSG00000118946 -0.6964719 6.9945080 -3.710494 0.0003985 0.1502070 PCDH17
ENSG00000146833 -1.7925956 2.0933749 -3.708006 0.0004018 0.1502070 TRIM4
ENSG00000238286 0.3957608 0.6291523 3.706382 0.0004040 0.1502070 SLC35E1P1
ENSG00000234719 -0.9946496 0.9947928 -3.679553 0.0004416 0.1608973 ENSG00000234719
ENSG00000222489 0.4179907 0.2003903 3.668398 0.0004582 0.1613770 ENSG00000222489
ENSG00000145736 -0.5293506 3.2139470 -3.666787 0.0004606 0.1613770 GTF2H2
ENSG00000234171 -0.3666779 2.5715243 -3.646265 0.0004929 0.1694146 ENSG00000234171
ENSG00000263535 -0.5471106 0.2504930 -3.637930 0.0005066 0.1696258 AK4P1
ENSG00000105963 -0.5320618 0.9723243 -3.629585 0.0005206 0.1696258 ADAP1
ENSG00000185518 -1.4407644 -0.7248376 -3.629134 0.0005214 0.1696258 SV2B
ENSG00000136104 0.3501590 3.8369805 3.609525 0.0005560 0.1735517 RNASEH2B
ENSG00000232300 0.5848956 -0.3102700 3.597250 0.0005788 0.1735517 FAM215B
ENSG00000266937 -0.2438614 1.6488055 -3.592392 0.0005880 0.1735517 ENSG00000266937
ENSG00000198932 -0.5232759 4.2805161 -3.590830 0.0005910 0.1735517 GPRASP1
ENSG00000105971 -0.4935931 4.8915284 -3.586868 0.0005987 0.1735517 CAV2
ENSG00000066382 1.6313657 3.2008651 3.586588 0.0005993 0.1735517 MPPED2
ENSG00000169436 2.9415822 -1.3911095 3.586128 0.0006002 0.1735517 COL22A1
ENSG00000022556 2.4000333 1.2777887 3.576075 0.0006201 0.1765254 NLRP2
ENSG00000227318 -1.7281778 -0.6086402 -3.568752 0.0006351 0.1772296 ENSG00000227318
ENSG00000170089 -0.4997211 2.3869475 -3.565386 0.0006421 0.1772296 ENSG00000170089
ENSG00000196993 -0.7658407 0.0667859 -3.556916 0.0006600 0.1794504 NPIPB9
ENSG00000217512 0.3593747 0.6649783 3.523761 0.0007347 0.1968282 ENSG00000217512
ENSG00000036448 0.7667332 1.7145378 3.512307 0.0007623 0.1976310 MYOM2
ENSG00000141837 -1.0014302 1.3880998 -3.507836 0.0007733 0.1976310 CACNA1A
ENSG00000269600 1.6893815 -1.3032529 3.507404 0.0007744 0.1976310 ENSG00000269600
ENSG00000169955 -0.6639366 1.6450844 -3.504748 0.0007811 0.1976310 ZNF747

Differential expression within each cell type

Compare logFC between celltypes

Genes with FDR < 20% within NPC or neuron separately

Neuron

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -3.6626244 -2.0458924 -5.049382 3.00e-06 0.0411363 ENSG00000230847
ENSG00000226259 -1.3519032 2.3980778 -4.951880 4.40e-06 0.0411363 GTF2H2B
ENSG00000162618 -2.4892764 -0.7365519 -4.841914 6.70e-06 0.0419231 ELTD1
ENSG00000164930 -0.8835409 4.8643554 -4.607514 1.62e-05 0.0765511 FZD6
ENSG00000177873 -0.5864374 3.6251045 -4.442837 2.99e-05 0.1129622 ZNF619
ENSG00000236725 -1.0954769 0.4658067 -4.232342 6.42e-05 0.1808377 ENSG00000236725
ENSG00000226002 0.7881767 0.1750937 4.220903 6.69e-05 0.1808377 ENSG00000226002

NPC

logFC AveExpr t P.Value qvalue gene
ENSG00000230847 -4.1265321 -2.0458924 -6.384328 0.00e+00 0.0002222 ENSG00000230847
ENSG00000173894 0.6179715 5.3493957 4.643534 1.41e-05 0.0871093 CBX2
ENSG00000115828 -1.6517356 0.6431161 -4.632172 1.48e-05 0.0871093 QPCT
ENSG00000164930 -0.8320215 4.8643554 -4.411670 3.35e-05 0.1482577 FZD6

Effect of correcting for Fibroblast score on case-control t-statistics in NPCs

We have demonstrated that correcting for the fibroblast score is important, especially in boosting concordance with HBCC. So what genes are affected by this correction? In order to test this, I compared the absolute value of the t-statstic (the test-statistic used compute the p-value) from the adjusted and unadjusted test.

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
tissue_exp_brain 495 29.13 85 2.92 1.703722e-19
CMC-modules_red 689 40.55 89 2.19 1.306218e-12
c5.GO_SYNAPSE_PART 549 32.31 74 2.29 1.522632e-11
c5.GO_SYNAPSE 677 39.85 85 2.13 1.977615e-11
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION 177 10.42 36 3.46 4.439413e-11
c5.GO_NEURON_PART 1088 64.04 117 1.83 7.934100e-11
c4.MODULE_47 196 11.54 37 3.21 2.288108e-10
secondary_FMRP-targets 770 45.32 90 1.99 2.311185e-10
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 9.71 33 3.40 4.544049e-10
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 20.42 51 2.50 1.252737e-09
c5.GO_PRESYNAPTIC_PROCESS_INVOLVED_IN_SYNAPTIC_TRANSMISSION 101 5.94 24 4.04 3.009981e-09
c2.MEISSNER_NPC_HCP_WITH_H3K4ME2 390 22.95 54 2.35 3.612506e-09
c5.GO_NEURON_PROJECTION 835 49.15 91 1.85 6.490311e-09
abnormal_motor_coordination_balance 458 26.96 59 2.19 1.054544e-08
c5.GO_NEUROTRANSMITTER_TRANSPORT 133 7.83 27 3.45 1.239876e-08

up only

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 15.10 46 3.05 1.583029e-11
CMC-modules_red 689 20.12 54 2.68 3.329240e-11
tissue_exp_brain 495 14.46 43 2.97 1.630936e-10
secondary_FMRP-targets 770 22.49 52 2.31 1.434069e-08
c2.BLALOCK_ALZHEIMERS_DISEASE_DN 1184 34.58 68 1.97 5.070287e-08
c5.GO_SYNAPSE 677 19.77 46 2.33 8.738854e-08
c5.GO_PRESYNAPTIC_PROCESS_INVOLVED_IN_SYNAPTIC_TRANSMISSION 101 2.95 15 5.09 2.271475e-07
c5.GO_SYNAPSE_PART 549 16.03 39 2.43 2.879986e-07
c4.MODULE_100 467 13.64 35 2.57 3.434816e-07
primary_PSD_(human_core) 644 18.81 43 2.29 3.811836e-07
c4.MODULE_66 474 13.84 35 2.53 4.881700e-07
kirov_psych.ed.set_mGluR5 37 1.08 9 8.33 8.584918e-07
kirov_synaptic.sets_mGluR5 37 1.08 9 8.33 8.584918e-07
primary_mGluR5 37 1.08 9 8.33 8.584918e-07
c2.REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES 159 4.64 18 3.88 9.357542e-07

downonly

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 4.89 23 4.70 6.649058e-10
tissue_exp_brain 495 14.68 42 2.86 8.851474e-10
c2.WONG_ADULT_TISSUE_STEM_MODULE 591 17.52 46 2.62 2.189234e-09
h.HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION 177 5.25 22 4.19 1.376309e-08
c2.MIKKELSEN_MEF_HCP_WITH_H3K27ME3 347 10.29 31 3.01 4.817120e-08
c2.SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 223 6.61 24 3.63 5.156047e-08
c2.CUI_TCF21_TARGETS_2_DN 744 22.06 50 2.27 5.305225e-08
c5.GO_NEURON_PART 1088 32.26 64 1.98 9.817372e-08
c2.DODD_NASOPHARYNGEAL_CARCINOMA_UP 1225 36.32 69 1.90 1.538746e-07
c5.GO_LEUKOCYTE_MEDIATED_IMMUNITY 94 2.79 14 5.02 6.656525e-07
c5.GO_LYMPHOCYTE_MEDIATED_IMMUNITY 69 2.05 12 5.86 7.622998e-07
c5.GO_CELL_PART_MORPHOGENESIS 556 16.49 38 2.30 1.544832e-06
c5.GO_B_CELL_MEDIATED_IMMUNITY 40 1.19 9 7.59 1.979220e-06
c5.GO_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS 867 25.71 51 1.98 2.241517e-06
c2.CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 397 11.77 30 2.55 2.781861e-06

Effect of correcting for Fibroblast score on case-control t-statistics in Neurons

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.REACTOME_RNA_POL_I_PROMOTER_OPENING 53 3.11 22 7.07 5.205652e-14
c2.REACTOME_AMYLOIDS 61 3.58 23 6.42 1.630978e-13
KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 79 4.64 26 5.60 1.805959e-13
c2.KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 80 4.70 26 5.53 2.528446e-13
kegg_Systemic_lupus_erythematosus 80 4.70 26 5.53 2.528446e-13
c5.GO_DNA_PACKAGING_COMPLEX 80 4.70 25 5.32 1.977977e-12
c2.REACTOME_PACKAGING_OF_TELOMERE_ENDS 41 2.41 18 7.48 3.281350e-12
KEGG_ALCOHOLISM 149 8.75 34 3.89 5.041777e-12
kegg_Alcoholism 149 8.75 34 3.89 5.041777e-12
CMC-modules_forestgreen 28 1.64 15 9.12 5.556191e-12
c2.REACTOME_RNA_POL_I_TRANSCRIPTION 78 4.58 24 5.24 7.968194e-12
c2.VERHAAK_GLIOBLASTOMA_PRONEURAL 165 9.69 35 3.61 2.248728e-11
c2.REACTOME_MEIOTIC_RECOMBINATION 71 4.17 22 5.28 5.078763e-11
c2.REACTOME_MEIOSIS 95 5.58 24 4.30 7.564072e-10
c2.REACTOME_TELOMERE_MAINTENANCE 67 3.93 20 5.08 8.074538e-10

up only

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
secondary_FMRP-targets 770 22.64 55 2.43 8.964789e-10
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 15.20 42 2.76 2.518142e-09
CMC-modules_red 689 20.25 48 2.37 2.541420e-08
c5.GO_CELL_PROJECTION 1508 44.33 80 1.80 1.172295e-07
c5.GO_CELL_PROJECTION_PART 809 23.78 51 2.14 2.186483e-07
c5.GO_SYNAPSE 677 19.90 45 2.26 2.751798e-07
kirov_psych.ed.set_mGluR5 37 1.09 9 8.27 9.066695e-07
kirov_synaptic.sets_mGluR5 37 1.09 9 8.27 9.066695e-07
primary_mGluR5 37 1.09 9 8.27 9.066695e-07
c2.WANG_LSD1_TARGETS_DN 31 0.91 8 8.78 2.282486e-06
primary_PSD_(human_core) 644 18.93 41 2.17 2.852382e-06
c5.GO_CYTOSKELETAL_PROTEIN_BINDING 693 20.37 43 2.11 3.130646e-06
cav2_Cav2::ALL 193 5.67 19 3.35 4.282863e-06
c2.BLALOCK_ALZHEIMERS_DISEASE_DN 1184 34.81 62 1.78 5.870449e-06
c4.MODULE_100 467 13.73 32 2.33 8.398773e-06

downonly

Gene Set Gene Set Size Expected Hits Observed Hits OR Pvalue
c2.REACTOME_RNA_POL_I_PROMOTER_OPENING 53 1.55 22 14.15 2.321068e-20
c2.REACTOME_AMYLOIDS 61 1.79 23 12.85 4.358139e-20
KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 79 2.32 25 10.79 1.461924e-19
c2.KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 80 2.35 25 10.65 2.069585e-19
c5.GO_DNA_PACKAGING_COMPLEX 80 2.35 25 10.65 2.069585e-19
kegg_Systemic_lupus_erythematosus 80 2.35 25 10.65 2.069585e-19
c2.REACTOME_RNA_POL_I_TRANSCRIPTION 78 2.29 23 10.05 2.526080e-17
c2.REACTOME_MEIOTIC_RECOMBINATION 71 2.08 22 10.56 3.831306e-17
CMC-modules_forestgreen 28 0.82 15 18.26 2.155808e-16
KEGG_ALCOHOLISM 149 4.37 29 6.64 3.733569e-16
kegg_Alcoholism 149 4.37 29 6.64 3.733569e-16
c5.GO_PROTEIN_DNA_COMPLEX 141 4.14 27 6.53 6.093019e-15
c5.GO_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC 89 2.61 22 8.43 7.612436e-15
c2.REACTOME_PACKAGING_OF_TELOMERE_ENDS 41 1.20 16 13.30 1.218042e-14
c5.GO_CHROMATIN_SILENCING 73 2.14 20 9.34 1.509248e-14

Effective sample size calculations

SessionInfo

## R version 3.3.2 (2016-10-31)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 14.04.5 LTS
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## attached base packages:
##  [1] grid      stats4    parallel  stats     graphics  grDevices datasets 
##  [8] utils     methods   base     
## 
## other attached packages:
##  [1] VennDiagram_1.6.17         futile.logger_1.4.3       
##  [3] ggbio_1.22.3               EnsDb.Hsapiens.v70_0.0    
##  [5] ensembldb_1.6.2            GenomicFeatures_1.26.2    
##  [7] WGCNA_1.51                 fastcluster_1.1.22        
##  [9] dynamicTreeCut_1.63-1      lmerTest_2.0-33           
## [11] lme4_1.1-12                Matrix_1.2-8              
## [13] pheatmap_1.0.8             GSEABase_1.36.0           
## [15] graph_1.52.0               annotate_1.52.1           
## [17] XML_3.98-1.5               AnnotationDbi_1.36.2      
## [19] HTSanalyzeR_2.26.0         igraph_1.0.1              
## [21] gage_2.24.0                GGally_1.3.0              
## [23] knitr_1.15.1               qvalue_2.6.0              
## [25] reshape2_1.4.2             xtable_1.8-2              
## [27] colortools_0.1.5           preprocessCore_1.36.0     
## [29] DESeq2_1.14.1              SummarizedExperiment_1.4.0
## [31] GenomicRanges_1.26.2       GenomeInfoDb_1.10.3       
## [33] IRanges_2.8.1              S4Vectors_0.12.1          
## [35] readr_1.0.0                latex2exp_0.4.0           
## [37] mixtools_1.0.4             ape_4.1                   
## [39] ggrepel_0.6.5              variancePartition_1.5.9   
## [41] Biobase_2.34.0             BiocGenerics_0.20.0       
## [43] ggplot2_2.2.1              gridExtra_2.2.1           
## [45] edgeR_3.16.5               limma_3.28.21             
## [47] synapseClient_1.14-2       doParallel_1.0.10         
## [49] iterators_1.0.8            foreach_1.4.3             
## 
## loaded via a namespace (and not attached):
##   [1] backports_1.0.5               AnnotationHub_2.6.4          
##   [3] Hmisc_4.0-2                   plyr_1.8.4                   
##   [5] lazyeval_0.2.0                splines_3.3.2                
##   [7] gmp_0.5-13                    BiocParallel_1.8.1           
##   [9] digest_0.6.12                 BiocInstaller_1.24.0         
##  [11] htmltools_0.3.5               GO.db_3.4.0                  
##  [13] gdata_2.17.0                  magrittr_1.5                 
##  [15] checkmate_1.8.2               memoise_1.0.0                
##  [17] BSgenome_1.42.0               cluster_2.0.5                
##  [19] prada_1.50.0                  Biostrings_2.42.1            
##  [21] matrixStats_0.51.0            colorspace_1.3-2             
##  [23] rrcov_1.4-3                   RCurl_1.95-4.8               
##  [25] genefilter_1.56.0             impute_1.48.0                
##  [27] VariantAnnotation_1.20.2      survival_2.40-1              
##  [29] gtable_0.2.0                  zlibbioc_1.20.0              
##  [31] XVector_0.14.0                RankProd_3.0.0               
##  [33] cellHTS2_2.38.0               Rmpfr_0.6-1                  
##  [35] DEoptimR_1.0-8                scales_0.4.1                 
##  [37] futile.options_1.0.0          vsn_3.42.3                   
##  [39] mvtnorm_1.0-5                 DBI_0.5-1                    
##  [41] Rcpp_0.12.10                  htmlTable_1.9                
##  [43] foreign_0.8-67                OrganismDbi_1.16.0           
##  [45] Formula_1.2-1                 htmlwidgets_0.8              
##  [47] httr_1.2.1                    gplots_3.0.1                 
##  [49] RColorBrewer_1.1-2            acepack_1.4.1                
##  [51] reshape_0.8.6                 nnet_7.3-12                  
##  [53] locfit_1.5-9.1                labeling_0.3                 
##  [55] munsell_0.4.3                 tools_3.3.2                  
##  [57] RSQLite_1.1-2                 evaluate_0.10                
##  [59] stringr_1.2.0                 yaml_2.1.14                  
##  [61] robustbase_0.92-7             caTools_1.17.1               
##  [63] KEGGREST_1.14.0               RBGL_1.50.0                  
##  [65] nlme_3.1-131                  mime_0.5                     
##  [67] BioNet_1.34.0                 biomaRt_2.30.0               
##  [69] compiler_3.3.2                pbkrtest_0.4-6               
##  [71] interactiveDisplayBase_1.12.0 png_0.1-7                    
##  [73] affyio_1.44.0                 tibble_1.2                   
##  [75] geneplotter_1.52.0            pcaPP_1.9-61                 
##  [77] stringi_1.1.2                 highr_0.6                    
##  [79] lattice_0.20-34               nloptr_1.0.4                 
##  [81] data.table_1.10.4             bitops_1.0-6                 
##  [83] httpuv_1.3.3                  rtracklayer_1.34.2           
##  [85] colorRamps_2.3                R6_2.2.0                     
##  [87] latticeExtra_0.6-28           affy_1.52.0                  
##  [89] KernSmooth_2.23-15            codetools_0.2-15             
##  [91] lambda.r_1.1.9                dichromat_2.0-0              
##  [93] boot_1.3-18                   MASS_7.3-45                  
##  [95] gtools_3.5.0                  assertthat_0.1               
##  [97] Category_2.40.0               rprojroot_1.2                
##  [99] rjson_0.2.15                  GenomicAlignments_1.10.0     
## [101] Rsamtools_1.26.1              rpart_4.1-10                 
## [103] minqa_1.2.4                   rmarkdown_1.3                
## [105] segmented_0.5-1.4             biovizBase_1.22.0            
## [107] shiny_1.0.0                   base64enc_0.1-3